US6121432A - Erythromycins - Google Patents

Erythromycins Download PDF

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Publication number: US6121432A
Authority: US; United States
Prior art keywords: methyl; formula; compound; dideoxy; carbon
Prior art date: 1998-04-08
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

US09/273,846

Other languages

English (en)

Inventor

Alain Bonnet

Francoise Gambier

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Aventis Pharma SA

Original Assignee

Hoechst Marion Roussel

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-04-08

Filing date

1999-03-22

Publication date

2000-09-19

1999-03-22 Application filed by Hoechst Marion Roussel filed Critical Hoechst Marion Roussel

1999-05-11 Assigned to HOECHST MARION ROUSSEL reassignment HOECHST MARION ROUSSEL ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BONNET, ALAIN, GAMBIER, FRANCOISE

2000-09-19 Application granted granted Critical

2000-09-19 Publication of US6121432A publication Critical patent/US6121432A/en

2001-02-01 Assigned to AVENTIS PHARMA S.A. reassignment AVENTIS PHARMA S.A. MERGER (SEE DOCUMENT FOR DETAILS). Assignors: ROUSSEL, HOECHST MARION

2019-03-22 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Natural products O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 24
239000002253 acid Substances 0.000 claims abstract description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
150000003839 salts Chemical class 0.000 claims abstract description 8
231100000252 nontoxic Toxicity 0.000 claims abstract description 6
230000003000 nontoxic effect Effects 0.000 claims abstract description 6
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims abstract description 4
229910052799 carbon Inorganic materials 0.000 claims abstract description 3
239000011203 carbon fibre reinforced carbon Substances 0.000 claims abstract description 3
238000000034 method Methods 0.000 claims description 6
238000002360 preparation method Methods 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 3
125000004432 carbon atom Chemical group C* 0.000 claims description 3
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 3
150000001412 amines Chemical class 0.000 claims description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 abstract description 2
101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 abstract 1
101150035983 str1 gene Proteins 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
239000000047 product Substances 0.000 description 21
239000000203 mixture Substances 0.000 description 16
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
238000001704 evaporation Methods 0.000 description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
230000008020 evaporation Effects 0.000 description 10
238000001035 drying Methods 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
238000000605 extraction Methods 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
239000000908 ammonium hydroxide Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
229960003276 erythromycin Drugs 0.000 description 4
239000000377 silicon dioxide Substances 0.000 description 4
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
238000001914 filtration Methods 0.000 description 3
RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 3
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
239000012043 crude product Substances 0.000 description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
238000004334 fluoridation Methods 0.000 description 2
CSYNQJPENMOLHR-UHFFFAOYSA-N n,n-diethylethanamine;ethyl acetate Chemical compound CCOC(C)=O.CCN(CC)CC CSYNQJPENMOLHR-UHFFFAOYSA-N 0.000 description 2
235000019980 sodium acid phosphate Nutrition 0.000 description 2
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
YLAXZGYLWOGCBF-UHFFFAOYSA-N 2-dodecylbutanedioic acid Chemical compound CCCCCCCCCCCCC(C(O)=O)CC(O)=O YLAXZGYLWOGCBF-UHFFFAOYSA-N 0.000 description 1
RVHOBHMAPRVOLO-UHFFFAOYSA-N 2-ethylbutanedioic acid Chemical compound CCC(C(O)=O)CC(O)=O RVHOBHMAPRVOLO-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
JVZPYJSJSQIEOG-UHFFFAOYSA-N 4-imidazol-1-ylbutan-1-amine Chemical compound NCCCCN1C=CN=C1 JVZPYJSJSQIEOG-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
101150108015 STR6 gene Proteins 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
CELPHAGZKFMOMR-UHFFFAOYSA-N azanium;dichloromethane;methanol;hydroxide Chemical compound [NH4+].[OH-].OC.ClCCl CELPHAGZKFMOMR-UHFFFAOYSA-N 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229910052681 coesite Inorganic materials 0.000 description 1
229910052906 cristobalite Inorganic materials 0.000 description 1
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
238000002955 isolation Methods 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
229940098895 maleic acid Drugs 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
238000011403 purification operation Methods 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
229910052682 stishovite Inorganic materials 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229960001367 tartaric acid Drugs 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
229910052905 tridymite Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins

Definitions

novel compounds of the invention are selected from the group consisting of ##STR2## wherein A is --OH and B forms with the 10-carbon a carbon--carbon double bond or A and B together form a carbonate or a carbamate, --OZ is selected from the group consisting of --OH, etherified hydroxy or esterified hydroxy and its non-toxic, pharmaceutically acceptable acid addition salts.
organic and inorganic acids suitable for the non-toxic, pharmaceutically acceptable acid addition salts are hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, acetic acid, propionic acid, trifluoroacetic acid, maleic acid, tartaric acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and especially stearic acid, ethylsuccinic acid or laurylsuccinic acid.
Z is hydrogen, ##STR3## or trimethylsilyl and R is alkyl of 1 to 6 carbon atoms.
Preferred compounds of formula I are ##STR4## and ##STR5## wherein Z is defined as above.
the process for the preparation of a compound of formula I comprises reacting a compound of the formula ##STR6## wherein A, B and --OZ are defined above with a fluoridation agent to obtain the compound of formula I, optionally releasing the 2'-hydroxyl and optionally esterifying or etherifying the 2'-hydroxyl and optionally forming A and B as a carbonate to form a compound of formula I A which optionally is subjected to an acid to form the acid addition salt.
the fluoridation agent may be N-fluoro-bis-(phenylsulfonyl)-imide of the formula ##STR7## or any other electrophilic agents.
strong bases such as tetrabutyl-ammonium fluoride when OZ is OSi(CH 3 ) 3 or alcohols such as methanol when OZ is COCH 3 .
the process of the invention for preparing a compound of the formula ##STR8## comprises reacting a compound of formula I with carbonyl-diimidazole to form a compound of the formula ##STR9## and reacting the latter with an amine of the formula
R is alkyl of 1 to 6 carbon atoms to obtain a compound of formula III and optionally releasing the 2'-hydroxyl.
the compounds of formula II are novel and particularly, 12-(oxycarbonylimidazol)-11-deoxy-10,11-didehydro-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl- ⁇ -L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-erythromycin-2'-acetoxy-2 ⁇ -fluoro.
Stage A 11-deoxy-10,11-didehydro-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl- ⁇ -L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-erythromycin.
Stage B 11-deoxy-10,11-didehydro-3-de[2,6-dideoxy-3-C-methyl-3-0-methyl- ⁇ -L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-erythromycin-2'-trimethylsilyloxy.
a mixture of 3.08 g of the product of the preceding stage, 340 mg of imidazole, 32 ml of anhydrous THF and 1.06 ml of hexamethyldisilylazane was stirred for 4 days at ambient temperature, followed by evaporation to dryness.
the residue was taken up in a mixture of 60 ml of methylene chloride and 60 ml of 0.5M sodium acid phosphate.
the reaction mixture was stirred for 15 minutes, followed by decanting, extraction with methylene chloride, drying and evaporating to dryness to obtain 3.345 g of the desired product.
Stage A 11-deoxy-10,11-didehydro-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl- ⁇ -L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-erythromycin-2 ⁇ -fluoro.
Stage B 11-deoxy-10,11-didehydro-3-de[(2,6-dideoxy-3-0-methyl- ⁇ -L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-erythromycin-2'-acetoxy-2 ⁇ -fluoro.
Stage C 12-(oxycarbonylimidazol)-11-deoxy-10,11-didehydro-3-de-[(2,6-dideoxy-3-C-methyl-3-0-methyl- ⁇ -L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-erythromycin-2'-acetoxy-2 ⁇ -fluoro.
Stage D 2'-acetoxy-11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl- ⁇ -L-ribohexopyranosyl)-oxy]-2 ⁇ -fluoro-6-0-methyl-3-oxo-12,11-[oxycarbonyl-[4-[4-(3-pyridinyl)-1H-imidazol-1-yl]-butyl]-imino]-erythromycin A.
Stage E 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl- ⁇ -L-ribohexopyranosyl)-oxy]-2 ⁇ -fluoro-6-0-methyl-3-oxo-12,11-[oxycarbonyl-[4-[4-(3-pyridinyl)-1H-imidazol-1-yl]-butyl]-imino]-erythromycin A.

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Biochemistry (AREA)
Biotechnology (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Saccharide Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

US09/273,846 1998-04-08 1999-03-22 Erythromycins Expired - Lifetime US6121432A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
FR9804366A FR2777282B1 (fr)	1998-04-08	1998-04-08	Nouveaux derives de la 2-fluoro 3-de((2,6-dideoxy 3-c-methyl 3-0-methyl-alpha-l-ribohexopyranosyl) oxyl) 6-o-methyl 3-oxo erythromycine, leur procede de preparation et leur application a la synthese de principes actifs de medicaments
FR9804366		1998-04-08

Publications (1)

Publication Number	Publication Date
US6121432A true US6121432A (en)	2000-09-19

Family

ID=9524992

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
US09/273,846 Expired - Lifetime US6121432A (en)	1998-04-08	1999-03-22	Erythromycins

Country Status (12)

Country	Link
US (1)	US6121432A (fr)
EP (1)	EP0949268B1 (fr)
JP (1)	JP4707785B2 (fr)
KR (1)	KR100633835B1 (fr)
CN (1)	CN1130370C (fr)
AT (1)	ATE256139T1 (fr)
DE (1)	DE69913413T2 (fr)
DK (1)	DK0949268T3 (fr)
ES (1)	ES2210999T3 (fr)
FR (1)	FR2777282B1 (fr)
HU (1)	HU227562B1 (fr)
PT (1)	PT949268E (fr)

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US6395710B1 (en)	1999-04-16	2002-05-28	Kosan Biosciences, Inc.	Macrolide antiinfective agents
US6399582B1 (en)	1999-04-16	2002-06-04	Ortho-Mcneil Pharmaceutical, Inc.	Ketolide antibacterials
US6451768B1 (en)	1999-04-16	2002-09-17	Kosan Biosciences, Inc.	Macrolide antiinfective agents
US6514944B2 (en)	1999-04-16	2003-02-04	Kosan Biosciences, Inc.	Macrolide antiinfective agents
US6590083B1 (en)	1999-04-16	2003-07-08	Ortho-Mcneil Pharmaceutical, Inc.	Ketolide antibacterials
US20030229031A1 (en) *	1999-05-24	2003-12-11	Pfizer Inc.	13-Methyl erythromycin derivatives
US6809080B2 (en)	2000-06-30	2004-10-26	Pfizer, Inc.	Macrolide antibiotics
US6833444B2 (en)	1999-01-27	2004-12-21	Pfizer, Inc.	Ketolide antibiotics
US6939861B2 (en)	1999-04-16	2005-09-06	Kosan Biosciences, Inc.	Amido macrolides
US20100216731A1 (en) *	2007-10-25	2010-08-26	Cempra Pharmaceuticals, Inc.	Process for the preparation of macrolide antibacterial agents
US20110195920A1 (en) *	2008-10-24	2011-08-11	Cempra Pharmaceuticals, Inc.	Biodefenses using triazole-containing macrolides
US8759500B2 (en)	2010-03-22	2014-06-24	Cempra Pharmaceuticals, Inc.	Crystalline forms of a macrolide, and uses therefor
US9051346B2 (en)	2010-05-20	2015-06-09	Cempra Pharmaceuticals, Inc.	Process for preparing triazole-containing ketolide antibiotics
US9200026B2 (en)	2003-03-10	2015-12-01	Merck Sharp & Dohme Corp.	Antibacterial agents
US9480679B2 (en)	2009-09-10	2016-11-01	Cempra Pharmaceuticals, Inc.	Methods for treating malaria, tuberculosis and MAC diseases
US9751908B2 (en)	2013-03-15	2017-09-05	Cempra Pharmaceuticals, Inc.	Convergent processes for preparing macrolide antibacterial agents
US9815863B2 (en)	2010-09-10	2017-11-14	Cempra Pharmaceuticals, Inc.	Hydrogen bond forming fluoro ketolides for treating diseases
US9861616B2 (en)	2013-03-14	2018-01-09	Cempra Pharmaceuticals, Inc.	Methods for treating respiratory diseases and formulations therefor
US9937194B1 (en)	2009-06-12	2018-04-10	Cempra Pharmaceuticals, Inc.	Compounds and methods for treating inflammatory diseases
US10188674B2 (en)	2012-03-27	2019-01-29	Cempra Pharmaceuticals, Inc.	Parenteral formulations for administering macrolide antibiotics

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Publication number	Priority date	Publication date	Assignee	Title
JP2001261694A (ja)	2000-03-06	2001-09-26	Pfizer Prod Inc	ケトライド抗生物質
WO2012076989A1 (fr)	2010-12-09	2012-06-14	Wockhardt Limited	Composés cétolides
CN106518939B (zh) *	2015-09-14	2019-12-31	江苏奥赛康药业有限公司	一种制备Solithromycin化合物的方法
CN106554381A (zh) *	2015-09-25	2017-04-05	苏州鹏旭医药科技有限公司	酮内酯类抗生素中间体及其制备方法和应用
EP3190122A1 (fr)	2016-01-08	2017-07-12	LEK Pharmaceuticals d.d.	Nouvelle voie synthétique vers du solithromycin et sa purification
CN106432383A (zh) *	2016-09-14	2017-02-22	重庆两江药物研发中心有限公司	索利霉素及其中间体的制备方法

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- 1999-03-30 JP JP08858099A patent/JP4707785B2/ja not_active Expired - Lifetime
- 1999-04-07 DE DE69913413T patent/DE69913413T2/de not_active Expired - Lifetime
- 1999-04-07 DK DK99400843T patent/DK0949268T3/da active
- 1999-04-07 AT AT99400843T patent/ATE256139T1/de active
- 1999-04-07 KR KR1019990011936A patent/KR100633835B1/ko not_active Expired - Lifetime
- 1999-04-07 PT PT99400843T patent/PT949268E/pt unknown
- 1999-04-07 HU HU9900958A patent/HU227562B1/hu unknown
- 1999-04-07 CN CN99104863A patent/CN1130370C/zh not_active Expired - Lifetime
- 1999-04-07 EP EP99400843A patent/EP0949268B1/fr not_active Expired - Lifetime
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US9453042B2 (en)	2007-10-25	2016-09-27	Cempra Pharmaceuticals, Inc.	Process for the preparation of macrolide antibacterial agents
US10131684B2 (en)	2007-10-25	2018-11-20	Cempra Pharmaceuticals, Inc.	Process for the preparation of macrolide antibacterial agents
US20100216731A1 (en) *	2007-10-25	2010-08-26	Cempra Pharmaceuticals, Inc.	Process for the preparation of macrolide antibacterial agents
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US8796232B2 (en)	2008-10-24	2014-08-05	Cempra Pharmaceuticals, Inc.	Methods for treating resistant diseases using triazole containing macrolides
US20110201566A1 (en) *	2008-10-24	2011-08-18	Cempra Pharmaceuticals, Inc.	Methods for treating resistant diseases using triazole containing macrolides
US9072759B2 (en)	2008-10-24	2015-07-07	Cempra Pharmaceuticals, Inc.	Biodefenses using triazole-containing macrolides
US20110195920A1 (en) *	2008-10-24	2011-08-11	Cempra Pharmaceuticals, Inc.	Biodefenses using triazole-containing macrolides
US9901592B2 (en)	2008-10-24	2018-02-27	Cempra Pharmaceuticals, Inc.	Methods for treating resistant diseases using triazole containing macrolides
US20110237534A1 (en) *	2008-10-24	2011-09-29	Cempra Pharmaceuticals, Inc.	Methods for treating gastrointestinal diseases
US9669046B2 (en)	2008-10-24	2017-06-06	Cempra Pharmaceuticals, Inc.	Biodefenses using triazole-containing macrolides
US9937194B1 (en)	2009-06-12	2018-04-10	Cempra Pharmaceuticals, Inc.	Compounds and methods for treating inflammatory diseases
US9480679B2 (en)	2009-09-10	2016-11-01	Cempra Pharmaceuticals, Inc.	Methods for treating malaria, tuberculosis and MAC diseases
US8975386B2 (en)	2010-03-22	2015-03-10	Cempra Pharmaceuticals, Inc.	Crystalline forms of a macrolide, and uses therefor
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Also Published As

Publication number	Publication date
EP0949268A1 (fr)	1999-10-13
JPH11310591A (ja)	1999-11-09
JP4707785B2 (ja)	2011-06-22
DK0949268T3 (da)	2004-03-29
FR2777282B1 (fr)	2001-04-20
DE69913413T2 (de)	2004-12-02
HUP9900958A1 (hu)	1999-11-29
ATE256139T1 (de)	2003-12-15
HU227562B1 (en)	2011-08-29
CN1235162A (zh)	1999-11-17
KR19990082977A (ko)	1999-11-25
KR100633835B1 (ko)	2006-10-13
DE69913413D1 (de)	2004-01-22
ES2210999T3 (es)	2004-07-01
PT949268E (pt)	2004-04-30
CN1130370C (zh)	2003-12-10
HUP9900958A3 (en)	2000-04-28
HU9900958D0 (en)	1999-06-28
FR2777282A1 (fr)	1999-10-15
EP0949268B1 (fr)	2003-12-10

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2000-09-01	STCF	Information on status: patent grant	Free format text: PATENTED CASE
2001-02-01	AS	Assignment	Owner name: AVENTIS PHARMA S.A., FRANCE Free format text: MERGER;ASSIGNOR:ROUSSEL, HOECHST MARION;REEL/FRAME:011497/0001 Effective date: 20010102
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